Usher syndrome type 1–associated cadherins shape the photoreceptor outer segment
Résumé
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to
retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are
microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus
tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15
(USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor
function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth,
and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of
Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed
markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development
and/or maintenance. We propose that calyceal processes, together with their associated links, control the
sizing of rod disks and cone lamellae throughout their daily renewal.
| Origine | Publication financée par une institution |
|---|
Loading...
